Introduction This proposal "Biological diversity: generation, control, and exploitation" is a successor to our previous proposal "Modular biology: experiment, theory and computation" which produced the Center for Modular Biology (CMB). We propose a natural continuation of our research on modules, which showed that these networks of interacting components are pervasive building blocks in biological systems. We will now ask how the existence of these building blocks restrains or enhances the generation of diversity. Like modularity, diversity is a fundamental property of biological systems that manifests itself at all levels of organization from molecules in a cell, through genetic diversity in a population, to species diversity in ecosystems. Our work will search for the organizing principles that underlie the generation and effects of diversity across the full range of scales of time and space. As with our previous grant, the heart of this endeavor lies in bringing together a group of scientists from a wide variety of disciplines who will meld experiment and theory to look for patterns and principles that illuminate this important biological problem. The core of this proposal is the group of Bauer Fellows, young scientists who will interact with each other and faculty research groups in ways that will substantially change their approach to science and send them out to act as intellectual leaders of the next generation of interdisciplinary research. We try to answer fundamental questions by synthesizing complementary approaches to biology: theory and experiment, molecular and phenomenological analysis, model and non-model organisms, laboratory and field populations, and high throughput surveys and detailed studies of individual examples. Our proposal seeks to meld the tools and approaches of evolutionary biology with molecular and cellular biology, since just as "nothing in biology makes sense except in the light of evolution" we are unlikely to make much sense of evolution without understanding the mutations, genes, biological functions, individuals, and populations that it acts on. This is especially true of biological diversity, which drives evolution, allows two genetically identical sister cells to behave in dramatically different ways, and plays a crucial role in the generation (cancer), protection from (adaptive immunity), and treatment of (pharmacogenetics) disease. The proposal uses different organisms, focuses on different levels of biological organization, and applies different techniques to study the diversity in biology. We believe that taking these complementary approaches within a unified team offers the best chance to reach a deep understanding of how diversity contrains and shapes biology.